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''' | ==Crystal structure of HIV-1 reverse transcriptase in complex with bulge-RNA/DNA and Nevirapine== | ||
<StructureSection load='4pwd' size='340' side='right' caption='[[4pwd]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4pwd]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PWD FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NVP:11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO[3,2-B 2,3-E][1,4]DIAZEPIN-6-ONE'>NVP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pqu|4pqu]], [[4puo|4puo]], [[3v4i|3v4i]], [[3v4d|3v4d]], [[3v81|3v81]], [[4q0b|4q0b]], [[1hys|1hys]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pwd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pwd RCSB], [http://www.ebi.ac.uk/pdbsum/4pwd PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In synthesizing a double-stranded DNA from viral RNA, HIV-1 reverse transcriptase (RT) generates an RNA/DNA intermediate. RT also degrades the RNA strand and synthesizes the second DNA strand. The RNase H active site of RT functions as a nuclease to cleave the RNA strand; however, the structural basis for endonucleolytic cleavage of the RNA strand remains elusive. Here we report crystal structures of RT-RNA/DNA-dATP and RT-RNA/DNA-nevirapine (NVP) ternary complexes at 2.5 and 2.9 A resolution, respectively. The polymerase region of RT-RNA/DNA-dATP complex resembles DNA/DNA ternary complexes apart from additional interactions of 2'-OH groups of the RNA strand. The conformation and binding of RNA/DNA deviates significantly after the seventh nucleotide versus a DNA/DNA substrate. Binding of NVP slides the RNA/DNA non-uniformly over RT, and the RNA strand moves closer to the RNase H active site. Two additional structures, one containing a gapped RNA and another a bulged RNA, reveal that conformational changes of an RNA/DNA and increased interactions with the RNase H domain, including the interaction of a 2'-OH with N474, help to position the RNA nearer to the active site. The structures and existing biochemical data suggest a nucleic acid conformation-induced mechanism for guiding cleavage of the RNA strand. | |||
Structures of HIV-1 RT-RNA/DNA ternary complexes with dATP and nevirapine reveal conformational flexibility of RNA/DNA: insights into requirements for RNase H cleavage.,Das K, Martinez SE, Bandwar RP, Arnold E Nucleic Acids Res. 2014 May 31. pii: gku487. PMID:24880687<ref>PMID:24880687</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Arnold, E.]] | |||
[[Category: Das, K.]] | |||
[[Category: Martinez, S E.]] | |||
[[Category: Connection]] | |||
[[Category: Dna-directed dna polymerase]] | |||
[[Category: Finger]] | |||
[[Category: Hydrolase-dna-rna-inhibitor complex]] | |||
[[Category: Nuclease]] | |||
[[Category: Nucleotidyltransferase]] | |||
[[Category: Palm]] | |||
[[Category: Ribonuclease h]] | |||
[[Category: Rna-directed dna polymerase]] | |||
[[Category: Rnase h]] | |||
[[Category: Thumb]] | |||
[[Category: Transferase]] | |||
[[Category: Trna]] | |||
Revision as of 10:53, 18 June 2014
Crystal structure of HIV-1 reverse transcriptase in complex with bulge-RNA/DNA and NevirapineCrystal structure of HIV-1 reverse transcriptase in complex with bulge-RNA/DNA and Nevirapine
Structural highlights
Publication Abstract from PubMedIn synthesizing a double-stranded DNA from viral RNA, HIV-1 reverse transcriptase (RT) generates an RNA/DNA intermediate. RT also degrades the RNA strand and synthesizes the second DNA strand. The RNase H active site of RT functions as a nuclease to cleave the RNA strand; however, the structural basis for endonucleolytic cleavage of the RNA strand remains elusive. Here we report crystal structures of RT-RNA/DNA-dATP and RT-RNA/DNA-nevirapine (NVP) ternary complexes at 2.5 and 2.9 A resolution, respectively. The polymerase region of RT-RNA/DNA-dATP complex resembles DNA/DNA ternary complexes apart from additional interactions of 2'-OH groups of the RNA strand. The conformation and binding of RNA/DNA deviates significantly after the seventh nucleotide versus a DNA/DNA substrate. Binding of NVP slides the RNA/DNA non-uniformly over RT, and the RNA strand moves closer to the RNase H active site. Two additional structures, one containing a gapped RNA and another a bulged RNA, reveal that conformational changes of an RNA/DNA and increased interactions with the RNase H domain, including the interaction of a 2'-OH with N474, help to position the RNA nearer to the active site. The structures and existing biochemical data suggest a nucleic acid conformation-induced mechanism for guiding cleavage of the RNA strand. Structures of HIV-1 RT-RNA/DNA ternary complexes with dATP and nevirapine reveal conformational flexibility of RNA/DNA: insights into requirements for RNase H cleavage.,Das K, Martinez SE, Bandwar RP, Arnold E Nucleic Acids Res. 2014 May 31. pii: gku487. PMID:24880687[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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